We have studied the response to growth factors (EGF, FGF and PGDF) and lipid metabolism in Syrian hamster embryo cell FGF was observed to stimulate the expression of PGHS-2 and mitogenesis. FGF did not enhance the metabolism of linoleic acid to 13-HODE. Some data suggest that prostaglandins were involved in FGF dependent mitogenesis but complete evidence is lacking. EGF-dependent mitogenesis was inhibited by lipoxygenase inhibitors but not attenuated by PGHS inhibitors. EGF did not stimulate prostaglandin formation but did stimulate the metabolism of linoleic acid to 13-HODE. The formation of 13-HODE is regulated by the tyrosine kinase activity of the EGF receptor but the mechanism is poorly understood. We used GG-MS techniques to measure the formation of endogenous 13-HODE. 13-HODE was detected in sufficient concentrations to enhance EGF-dependent mitogenesis. The linoleic acid metabolites potentiated EGF-dependent mitogenesis in the supB+ SHE cells but not in the supB-. We have also examined the structural characteristics necessary for enhancing EGF mitogenesis. We have transfected normal SHE fibroblasts with plasmid DNA vectors containing the retroviral v-erbB oncogene or its cellular homolog c-erbB-2 and established stable transfected cell lines. erbB-Transfected cells demonstrate increased lipoxygenase metabolism of both linoleic and arachidonic acid. We have started to examine the metabolism of linoleic and arachidonic acid in a variety of human breast carcinoma cell lines which vary in their expression of EGF receptor, c-erbB-2/HER2, and estrogen receptor. We have observed a close association between high levels of c-erbB-2 and EGF receptor expression and the extent of linoleic acid metabolism in these cells. Inhibition of lipoxygenase metabolism attenuates DNA synthesis in the erbB-2/EGFR overexpressing cells.